- ADENINE DERIVATIVES WHICH ARE USEFUL IN THE TREATMENT OF ALLERGIC DISEASES OR OTHER INFLAMMATORY CONDITIONS
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Compounds of formula (I).
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Page/Page column 30
(2016/06/13)
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- Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives
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We report the synthesis and biological evaluation of a new series of 8-oxoadenines substituted at the 9-position with a 4-piperidinylalkyl moiety. In vitro evaluation of the piperidinyl-substituted oxoadenines 3a-g in human TLR7- or TLR8-transfected HEK293 cells and in human PBMCs indicated that TLR7/8 selectivity/potency and cytokine induction can be modulated by varying the length of the alkyl linker. Oxoadenine 3f containing a 5-carbon linker was found to be the most potent TLR7 agonist and IFNα inducer in the series whereas 3b possessing a 1-carbon linker was the most potent TLR8 agonist.
- Bazin, Hélène G.,Li, Yufeng,Khalaf, Juhienah K.,Mwakwari, Sandra,Livesay, Mark T.,Evans, Jay T.,Johnson, David A.
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p. 1318 - 1323
(2015/04/14)
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- NOVEL COMPOSITIONS AND METHODS FOR TREATMENT OF DISEASES RELATED TO ACTIVATED LYMPHOCYTES
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The present invention relates to inhibiting proliferation and inducing apoptosis in activated lymphocytes, including T cells and B cells. The invention also provides compositions and methods for inhibiting proliferation and inducing apoptosis in activated lymphocytes, as well methods for treating diseases associated with activated lymphocytes by administering 5-HT receptor antagonists.
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Page/Page column 58-59
(2008/06/13)
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- ARYLAMIDINE DERIVATIVE, SALT THEREOF AND ANTIFUNGAL CONTAINING THESE
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An arylamidine derivative represented by the general formula (wherein R 1 represents optionally protected or substituted amidino; and R 2 and R 3 are the same or different and each represents hydrogen or halogeno) or a salt of the derivative. The derivati
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Page/Page column 23
(2008/06/13)
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- PHARMACEUTICAL COMPOSITION AND METHOD USING ANTIFUNGAL AGENT IN COMBINATION
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A pharmaceutical composition containing one or more antifungal agents selected from an arylamidine derivative represented by the general formula: (wherein R1 represents an amidino group that may be substituted with a hydroxyl group that may be
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Page/Page column 11
(2008/06/13)
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- Indole nitriles
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Compounds of the formula (I) wherein m, n, R1, R2, R3, R4, R5 and R6 are as described herein, together with methods for making the compounds and using the compounds for treatment of diseases or conditions mediated by Cathepsin K.
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- Synthesis of Nitro Esters of Prednisolone, New Compounds Combining Pharmacological Properties of Both Glucocorticoids and Nitric Oxide
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Glucocorticoids (GC) are widely used in therapy for their many pharmacological properties including antiinflammatory and immunosuppressive actions. However, their use over long periods is hampered by a number of severe side effects. Given the biological properties of nitric oxide (NO) and previous experience with nonsteroidal antiinflammatory agents, we synthesized new chemical entities combining both NO and GC properties. Here we report the synthesis of nitro esters of prednisolone obtained through the esterification, with different linkers, on the hydroxy group at C-21 position of the corticosteroid structure. The alkyl chain, as of the nitrooxy derivative (2), or aromatic linkers, as of o-, m-, and p-nitrooxymethylbenzoate derivatives (3-5), respectively, furnish stable compounds that release NO and inhibit the GC receptors in biological assays. To improve solubility we introduced a more water-soluble linker such as the nitrooxyalkylpiperidine or -piperazine group (6-9). Also these compounds retained properties of both NO and prednisolone. Compound 5 (NCX 1015) was selected for its better profile: enhanced antiinflammatory properties and reduced side effects compared with prednisolone. NCX 1015 is currently under preclinical development.
- Baraldi, Pier Giovanni,Romagnoli, Romeo,Nu?ez, Maria Del Carmen,Perretti, Mauro,Paul-Clark, Mark J.,Ferrario, Massimiliano,Govoni, Mirco,Benedini, Francesca,Ongini, Ennio
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p. 711 - 719
(2007/10/03)
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- Synthesis of cyclic prodrugs of Aggrastat and its analogue with a modified phenylpropionic acid linker
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(formula presented) 1a, n=2; 1b, n=1 The objective of this work was to synthesize cyclic prodrugs 1a and 1b from Aggrastat 2a and its analogue 2b, respectively, to improve their membrane permeation. Cyclic prodrugs 1a and 1b were formed using an ester bond between the -COOH group of Aggrastat or its analogue and the phenylpropionic acid linker 3 and an amide bond between the piperidinylamine and the -COOH group of the linker 3, respectively, as outlined in Scheme 4.
- Song, Xiaoping,He, Henry T.,Siahaan, Teruna J.
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p. 549 - 552
(2007/10/03)
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- Rapid parallel synthesis applied to the optimization of a series of potent nonpeptide neuropeptide Y-1 receptor antagonists
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This study describes the integrated application of parallel synthesis and computational chemistry to the design of potent nonpeptide antagonists for the neuropeptide Y-1 (NPY1) receptor. A lead molecule was modeled in the active site of the NPY1 receptor, and a potentially fruitful region for analog construction was identified. Synthesis of suitable scaffolds followed by solution phase generation of a small library of analogs produced a compound with 5-fold improvement in binding over the already potent lead. This new compound was shown to be an unanticipated side product of the parallel synthesis reaction.
- Siegel, Miles G.,Chaney, Michael O.,Bruns, Robert F.,Clay, Michael P.,Schober, Douglas A.,Van Abbema, Anne M.,Johnson, Douglas W.,Cantrell, Buddy E.,Hahn, Patric J.,Hunden, David C.,Gehlert, Donald R.,Zarrinmayeh, Hamideh,Ornstein, Paul L.,Zimmerman, Dennis M.,Koppel, Gary A.
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p. 11619 - 11639
(2007/10/03)
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